General
Preferred name
TECOVIRIMAT
Synonyms
ST-246 ()
TECOVIRIMAT MONOHYDRATE ()
Arestvyr, SIGA-246, ST-246, TPOXX ()
Tpoxx ()
SIGA-246 ()
ST 246 ()
P&D ID
PD058740
CAS
869572-92-9
816458-31-8
Tags
available
drug
Approved by
EMA
FDA
First approval
2018
Drug Status
investigational
approved
Drug indication
Virus infection
Smallpox
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
MOA
Tecovirimat inhibits the production of extracellular viral forms, which are responsible for the systemic spread of infection, inhibiting virus-induced cytopathic effects. Tecovirimat does not inhibit the formation of intracellular forms of the virus (IMV); however, by inhibiting envelopment, and therefore preventing the exit of viral particles from an infected cell, the smallpox infection is slowed to a point where the immune system can eliminate the virus [F619].; ; Tecovirimat has shown a high level of selectivity and specificity for orthopoxviruses. Tecovirimat targets the viral p37 protein, a highly conserved protein with no homologs outside of the Orthopoxvirus genus, inhibiting its function that is necessary for required for the viral envelopment of IMV (intracellular mature virus). Tecovirimat interferes with the cellular localization of p37 viral protein and prevents its association with cellular proteins involved in membrane trafficking [F619].
ABSORPTION
Readily absorbed following oral administration, with mean times to maximum concentration from 3 to 4 h [A35133].; A study was conducted to determine the safety, tolerability, and pharmacokinetics of ST-246 administered as a single daily oral dose. Steady state was reached by day 6 (within 3 to 5 half-lives)[A35134].
METABOLISM
In vitro studies indicate that tecovirimat is not a substrate of major cytochrome P450 (CYP) enzymes, but it is a substrate of human recombinant UGTs (specifically of UGT1A1 and 1A4) [FDA label].; ; Tecovirimat was found to be metabolized into 3 most abundant metabolites, M4, M5 and TFMBA, which do not have pharmacological activity [FDA label].
TOXICITY
Tecovirimat has demonstrated to be well tolerated, with no serious adverse events (AEs). Common adverse reactions in healthy adult subjects (⥠2%) were headache, nausea, abdominal pain, and vomiting [FDA label], [A35143].; ; Co-administration of repaglinide and tecovirimat may cause mild to moderate hypoglycemia [FDA label].; ; Oral administration of tecovirimat is generally well-tolerated at dose levels up to 2,000 mg/kg/day (mice) [F619].
PHARMACODYNAMICS
Tecovirimat prevents viral spread throughout the body [F619].; This drug inhibits its molecular target, a protein called p37, from interacting with intracellular transport components necessary for the production of enveloped virus, and therefore the spread of virus [F619].;
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
0
Organisms
6
Compound Sets
14
ChEMBL Approved Drugs
ChEMBL Drugs
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
MedChem Express Bioactive Compound Library
NCATS Inxight Approved Drugs
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
27
Molecular Weight
376.1
Hydrogen Bond Acceptors
3
Hydrogen Bond Donors
1
Rotatable Bonds
2
Ring Count
6
Aromatic Ring Count
1
cLogP
2.4
TPSA
66.48
Fraction CSP3
0.42
Chiral centers
6.0
Largest ring
6.0
QED
0.64
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Pathway
Proteases/Proteasome
Anti-infection
Target
Cysteine Protease
Arenavirus
Orthopoxvirus
Antiviral
Indication
smallpox
MOA
orthopoxvirus egress inhibitor
Source data
